In this Q&A, Matt Zibelman, MD, a fellow at Fox Chase Cancer Center in Philadelphia, discusses research in genitourinary cancer that was presented at the 2014 American Society of Clinical Oncology Annual Meeting.

Session Chair: Sumanta Kumar Pal, MD, City of Hope, Duarte, CA


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  • Robert J. Motzer, MD, Memorial Sloan Kettering Cancer Center (discussant)
  • Asim Amin, MD, PhD, Levine Cancer Institute (discussant)
  • Lauren Christine Harshman, MD, Dana-Farber Cancer Institute, Boston, MA
  • Thomas Powles, MBBS, MRCP, MD, Barts Cancer Institute, Queen Mary University Hospital of London, England
  • Toni K. Choueiri, MD, Dana-Farber Cancer Institute, Boston, MA (discussant)
  • Padmanee Sharma, MD, PhD, The University of Texas MD Anderson Cancer Center, Houston, TX

What was the focus of this educational session?

The discussion of “unleashing the immune system” in this session was geared primarily toward the use of PD and PD-L1 inhibition in both renal cell carcinomas and in bladder cancer. Prior to this talk, we hadn’t heard a lot of discussion about PD and PD-L1 immunotherapy in bladder cancer, so this was one of the exciting parts of this presentation.

Can you talk about some of the science that was presented?

Dr. Powles’s abstract (abstract #5011) was about one of the new PD-L1 targeting drugs—specifically MPDL3280A— and its use in a phase 1 study in patients with advanced bladder cancer.  The study results suggested that targeting the PD-1/PD-L1 pathway offers promising activity in a disease that is often not responsive to a lot of other therapies, and in a group of patients that often have an abundance of co-morbid conditions. Dr. Powles mentioned during the talk that the drug had been granted FDA breakthrough designation as of May 31, 2014, adding an additional layer of excitement to  the presentation as well.

RELATED: Renal Cell Carcinoma Research Center

Dr. Motzer spoke about the use of nivolumab in RCC patients at different dose levels (abstract #5009), comparing responses and toxicities at various doses.  The biggest take-home was that there does not seem to be a real strong dose-related response—patients appear to have responses at all dose levels, although there was some indication that overall survival was a little better at the higher doses.  However, these results were still early and the number of patients too small to say that definitively. In addition, toxicities did not seem to really differ significantly at the higher dose levels.

The continued search for reliable biomarkers for PD/PD-L1 therapy was one of the other big topics discussed. The second discussant, Dr. Sharma, did a thorough job providing an overview of the search for useful biomarkers with these drugs, and discussing whether PD-L1 will ultimately be established as a biomarker for the PD-1 inhibitors. While PD-L1 expression seems to correlate with better responses, there are definitely patients with PD-L1-negative tumors who garner a significant response, albeit these patients are somewhat less likely to respond.  Dr. Sharma made some salient points about the heterogeneity of tumor samples, both intratumoral and between primary tumors and metastatic sites, as well as other potentially relevant factors, such as the impact of previous therapies and timing in the disease course.   Additionally, there may be other factors, such as tumor infiltrating lymphocytes in the tumor microenvironment, which may prove to be better indicators of tumor response. 

Matt Zibelman, MD, is a fellow at Fox Chase Cancer Center in Philadelphia, PA.